The Viral Vector Core will function as an integral part of the gene therapy for cancer program in that it will interact with and provide reagents to the three proposed projects. The role of the Core in the program is to function as a dynamic resource that will utilize state-of- the-art vector technology to efficiently deliver and express therapeutic genes into various cells types as well as develop novel vectors that can potentially improve our ability to treat human disease by gene therapy. Given the requirement of the three projects for high efficiency gene transduction and subsequent expression, the development of vectors that can express therapeutic genes at high levels or infect certain cell types is absolutely essential. The Vector Core was established in January 1991 by start-up funds provided by the Pittsburgh Transplant Institute, the Pittsburgh Cancer Institute, and the Pittsburgh Genetics Institute and was designed to function both as a service facility as well as a research and development facility. The Core was established to support the program for model systems for gene therapy and to provide support to other gene therapy projects such as this program in gene therapy for cancer. In this capacity, the Core has generated viral vectors and provide reagents to projects working on treatment of Gaucher disease, gene therapy for arthritis, gene transfer to facilitate islet transplantation, gene therapy for treatment of brain cancer, gene transfer to hepatocytes, and gene therapy for cancer. The Vector Core has also provided beta-galactosidase (LacZ) expressing marker viruses to investigators to infect neuronal cells, hepatocytes, islets synoviocytes, T-cells, activated NK cells and fibroblasts. The Core has served as a hub for the gene therapy projects for the last three and a half years and thus is a fully functional Core Facility. The Core is working with three types of viral systems, retroviral, adenoviral and adeno-associated viral vectors, for delivery of DNA to cells both in culture and in vivo. The ability of the Vector Core to provide three different functional viral delivery systems allows for a greater probability of efficiently transducing the therapeutic gene of interest into the appropriate target cell. The Core also serves as a training facility for individuals who are interested in utilizing viral systems in their gene therapy experiments. Thus the Vector Core will closely interact with the three proposed gene therapy for cancer projects to provide information, vectors, marker viruses, cell lines, and new vector systems.